National Institute of Mental Health (NIMH)
National Cancer Institute (NCI)
National Eye Institute (NEI)
National Human Genome Research Institute (NHGRI)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute on Drug Abuse (NIDA)
National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of General Medical Sciences (NIGMS)
National Center for Complementary and Integrative Health (NCCIH)
National Center for Advancing Translational Sciences (NCATS)

Funding Opportunity Title

Development of Highly Innovative Tools
and Technology for Analysis of Single Cells (SBIR) (R43/R44)

This funding opportunity announcement (FOA) encourages
Small Business Innovation Research (SBIR) grant applications from small
business concerns (SBCs) to develop and validate next-generation single cell
analysis technologies and tools. The purpose is to foster the
commercialization of innovative single cell analysis technologies for their
broad use in biomedical research. The novel single-cell analysis technologies
will aid in obtaining a fine-grained and dynamic view of heterogeneous
cellular states and intercellular interactions, thereby providing new
mechanistic insight into biological processes in health and
disease. Applications should define the current state of technologies
and tools as a benchmark against which the new approach(es) will be
measured. The new approach(es) should provide substantially improved
performance in sensitivity, selectivity, spatiotemporal resolution,
scalability, multiplexing capability, or non-destructive analysis of molecular
or functional measures of single cells.

A companion FOA to support STTR Grants is also available
see PA-17-148

Key Dates

Posted Date

February 1, 2017

Open Date (Earliest Submission Date)

March 5, 2017

Letter of Intent Due Date(s)

Not applicable

Application Due Date(s)

Standard
dates apply , by 5:00 PM local time of applicant organization.

*** Note new SBIR/STTR Standard Due Dates.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

It is critical that applicants follow the SBIR/STTR (B) Instructions
in the SF424
(R&R) SBIR/STTR Application Guide except where instructed to do
otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any
program-specific instructions noted in Section
IV. When the program-specific instructions deviate from those in the
Application Guide, follow the program-specific instructions. Applications that
do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and
Department of Health and Human Services partners. You must use one of these submission
options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online.

Single cell analysis has recently become an active area of
research to uncover fundamental biological principles behind cell diversity,
which are often masked and not amenable to the population analysis of cells.
The past several years have witnessed a rapid advancement in the development of
single cell technologies and analysis methods. Multiple single cell "-omics"
approaches are emerging that provide unprecedented high resolution of molecular
signatures of a cell. The ability to measure genomic, epigenomic,
transcriptomic, and metabolic status in individual cells are expected to
provide new insight into molecular pathways in health and disease. In addition,
powerful technologies are being developed to isolate and analyze rare cells
from a heterogeneous population and to examine distinct cellular states in
complex tissue environments. Several NIH programs have recently strengthened
the support of single cell research and technology development, including the
NIH Common Fund Single Cell Analysis Program (SCAP) (http://commonfund.nih.gov/singlecell/)
and BRAIN initiative (http://www.braininitiative.nih.gov).
This funding opportunity announcement (FOA) intends to add the support and
address key roadblocks in single cell analysis research by facilitating the
commercialization of the innovative single cell analysis technologies and
tools. A goal is to accelerate the development and translation of the
cutting-edge single cell analysis approaches. The NIH expects that the
commercialization of the advanced single cell technologies and tools will help
expedite biomedical research and advance precision medicine to the cellular
level by generating new knowledge on cellular heterogeneity, cellular
organization and communication rules, as well as emergent properties. Here, NIH
calls on the small business community to generate highly innovative
technologies and tools that will assist with this goal.

Objectives

This FOA encourages applications to develop next-generation
technologies and tools to better define cell heterogeneity and organizational
rules. The innovative approaches should provide new analytical measures and
manipulations of: cellular contents, structure, and activity at the single cell
level significantly beyond those currently available. The objectives are to
accelerate the development and translation of promising concepts by focusing on
overcoming technical challenges, building prototype systems, and generating
novel tools toward commercialization. This FOA seeks to support innovative
projects that will result in robust tools and approaches widely adoptable and
usable by the research community through the marketplace. Toward this end,
applications that draw upon diverse expertise from both within and outside
(e.g., engineering, physics, chemistry, computation) of biology are of
particular interest. To the extent that it is useful in combining different
types of expertise, applications with multiple Program Directors/Principal
Investigators are encouraged (See http://grants.nih.gov/grants/multi_PI/).

Applications can propose high-impact technologies that
include but are not limited to:

Although applications will not be restricted to a particular
type of technology, NIH is especially interested in applications to develop
next-generation approaches that can or have the potential to distinguish
heterogeneous states among cells in
situ or in clinically relevant samples.

Well-established biological assay(s) and positive control
experiments should be included for proof-of-concept testing and validation of
the innovative technologies and tools. Potential pitfalls of the experimental
measurements must be clearly discussed and minimized accordingly. Single cell
analysis methods should address signal-to-noise issue and strive to reduce
technical noise by optimizing experimental processes. Applicants are expected
to evaluate and interpret “noise” of the measurements, which can have both
technical and biological origins. Methods and analyses should take into account
the sample source variability and the inherently dynamic nature of biological processes
such as cell cycle and developmental plasticity, which may complicate the
interpretation of the measurements.

It is important to emphasize that the topics listed above
are only meant to be illustrative, and not meant to be a comprehensive list of
appropriate topics, nor exclusive of other appropriate topics. Applications may
propose projects that are highly innovative or that are enhancements of current
approaches. In either case, studies must significantly advance the current
state of the art of single cell analysis and have commercial potential.
Submitted applications should be aligned with the research priorities of at
least one of the participating ICs (see below and Part 1). Potential applicants
are strongly encouraged to contact Scientific/Research
Contact(s) before submitting an application.

The NIMH intends to support the development of single cell
technologies to advance the mission of the Institute as described in the NIMH
Strategic Plan. In particular the NIMH is interested in the next-generation
approaches that can or have the potential to distinguish heterogeneous states
of brain cells in
mammalian and human brain samples (e.g., NIH NeuroBioBank).

NCI

Tumors are highly heterogeneous at the cellular, molecular,
and genetic levels. Through this FOA, the NCI is especially interested in
applications for novel tools/technologies that enable the characterization of
this heterogeneity among cells in situ or in clinically relevant samples
and for clinically testing drug combinations and resistance with minimal
invasiveness. These tools/technologies include but are not limited to
multidimensional single cell imaging, single cell mass cytometry, high
throughput technologies for isolation and characterization of DNA and RNA from
individual cells either in situ or in clinically relevant samples.

NIDA supports research to understand, prevent, and treat
substance use disorders and mitigate their consequences to public health. For
this FOA, NIDA encourages basic and/or clinical collaborative research to
promote the understanding of mechanisms of neuronal differentiation, neural
circuit formation and modulation, synaptic formation, trimming and activities,
as well as related events of brain development pertinent to substances of
abuse, including but not limited to nicotine, amphetamine, cocaine, opiates,
barbiturates, cannabinoids, and hallucinogens. Specifically, for this program
announcement, NIDA is interested in the identification of genetic and
epigenetic effects on the development and function of the nervous system, as
well as novel approaches to elucidate the processes and genetic mechanisms
involved in the development of brain regions, neural circuits, and
neurotransmitter systems mediating the addictive properties of drugs of abuse
to inform future prevention and treatment of substance use disorders. Please
note: NIDA does not support Phase IIB applications, or Phase IIB research, for
this announcement.

NIGMS

The NIGMS supports basic biomedical research and research
training that contributes to the understanding of fundamental cellular and
physiological principles, and specific clinical areas (i.e., clinical
pharmacology, trauma and burn injury, sepsis, wound healing, and
anesthesiology). The four NIGMS divisions support research and technology
development in basic cell biology, biophysics, biochemistry, chemistry,
genetics, developmental biology, pharmacology, trauma, burn, wound healing and
sepsis. Please see the NIGMS Program
Descriptions and Research Topics for more detailed information.

NIDCR

NIDCR supports research and research training to improve
dental, oral and craniofacial (DOC) health. For a full spectrum of our
research interests, please consult NIDCR Strategic
Plan 2014-2019. Relevant to this FOA, high priority will be placed on
the application of tools and technologies to differentiate benign, malignant
and metastasizing oral or salivary gland cancer cells, detect malignant
transformation of oral epithelial cell including human papillomavirus
(HPV)-positive and HPV-negative status, identify and characterize
stem/progenitor cells for DOC tissue regeneration, and trace cell fates and
lineages of DOC cells along developmental, degeneration and regeneration
pathways.

NIDDK

NIDDK is interested in applications for the development of
novel tools/technologies with single cell resolution able to generate precise
data in the following areas:

a) Better understanding of pancreatic islet function
and dysfunction through the identification of local alterations or cellular
signatures in the islet and extra-islet environment that are associated with
islet cell plasticity, diabetes pathogenesis, progression or response to
treatment and may lead to the discovery of novel cellular or molecular
therapeutic targets; study of cell subtypes in other tissues/organs involved in
the development and progression of diabetes and other endocrine diseases and
their complications. These include analysis of cell diversity of the immune
system, adipose tissue, muscle, liver, gut, nervous system and their
interactions to better understand initiation, progression and/or heterogeneity
of the disease in humans.

b) Isolating and interrogating single cells from
normal or diseased tissues of the alimentary gastrointestinal tract, liver,
biliary system, and exocrine pancreas.

c) Isolating and interrogating single cells from
normal or diseased kidney, lower urinary tract, including the urinary bladder,
prostate, or hematopoietic stem cell niche, or techniques to be used by the
Kidney Precision Medicine Project consortium.

Relevant proposals may include but are not limited to the
development or improvement of multidimensional single cell imaging, single cell
mass cytometry protocols and high throughput technologies for the multi-omics
exploration of individual cells either in situ or in clinically relevant
samples. For a description of disease areas relevant to the NIDDK, please refer
to https://www.niddk.nih.gov/research-funding/research-programs/Pages/default.aspx.

NIEHS

NIEHS supports research on how the environment affects
people in order to promote healthier lives. For this FOA, NIEHS is interested
in tools and technologies to detect responses to environmental stressors in
heterogeneous populations of cells, approaches to detect effects of
environmental stress on germ cells, and technologies to isolate or detect
effects in stem or progenitor cells. Please see the NIEHS Program
Descriptions and Research Topics for more detailed information.

NCCIH

National Center for Complementary and Integrative Health
(NCCIH) is interested in supporting research that will develop highly
innovative tools and technology for analysis of single cells in response to
natural products, their metabolic derivatives, probiotics, or prebiotics at
genetic/genomic, epigenetic/epigenomic, metabolomic, or other molecular and
cellular levels.

NEI

The NEI supports biomedical research and research training
to understand the visual system, a major component of the human brain. Loss of
neurons or various cell types in the retina or the brain can cause visual
impairment. NEI is interested in applications for the development of novel
tools/technologies with single cell resolution that can improve our understanding
in all cell types in the visual system, and how they connect with each other.
For a description of the NEI SBIR/STTR research priorities, please refer to https://nei.nih.gov/funding/smallbusiness_nei.

The number of awards is contingent upon NIH appropriations
and the submission of a sufficient number of meritorious applications.

Award Budget

According to statutory guidelines, total funding support
(direct costs, indirect costs, fee) normally may not exceed $150,000 for
Phase I awards and $1,000,000 for Phase II awards. With appropriate
justification from the applicant, Congress will allow awards to exceed these
amounts by up to 50% as a hard cap ($225,000 for Phase I and $1,500,000 for
Phase II). However, NIH has received a waiver from SBA, as authorized by
statute, to exceed the hard cap of $225,000 for Phase I or $1,500,000 for
Phase II for specific topics. The current list of approved topics can be
found at https://sbir.nih.gov/funding#omni-sbir.
Note: Many single cell-relevant topics are listed as approved topics. Applicants
are strongly encouraged to contact NIH program officials prior to
submitting any application in excess of the guidelines and early in the
application planning process. In all cases, applicants should propose a
budget that is reasonable and appropriate for completion of the research
project.

Durations up to two years for Phase I and up to three
years for Phase II may be requested.

NIH grants policies as
described in the NIH
Grants Policy Statement will apply
to the applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Only United States small business concerns (SBCs) are
eligible to submit applications for this opportunity. A
small business concern is one that, at the time of award of Phase I and Phase
II, meets all of the following criteria:

1. Is organized for
profit, with a place of business located in the United States, which operates
primarily within the United States or which makes a significant contribution to
the United States economy through payment of taxes or use of American products,
materials or labor;

2. Is in the legal
form of an individual proprietorship, partnership, limited liability company,
corporation, joint venture, association, trust or cooperative, except that
where the form is a joint venture, there must be less than 50 percent
participation by foreign business entities in the joint venture;

3.

i. SBIR
and STTR. Be a concern which is more than 50% directly
owned and controlled by one or more individuals (who are citizens or permanent
resident aliens of the United States), other business concerns (each of which
is more than 50% directly owned and controlled by individuals who are citizens
or permanent resident aliens of the United States), or any combination of
these; OR

ii. SBIR-only.
Be a concern which is more than 50% owned by multiple venture capital operating
companies, hedge funds, private equity firms, or any combination of
these. No single venture capital operating company, hedge fund, or
private equity firm may own more than 50% of the concern; OR

iii. SBIR and
STTR. Be a joint venture in which each entity to the
joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii)
of this section. A joint venture that includes one or more concerns that meet
the requirements of paragraph (ii) of this section must comply with §
121.705(b) concerning registration and proposal requirements.

4. Has, including
its affiliates, not more than 500 employees.

If the concern is more than 50% owned by multiple venture
capital operating companies, hedge funds, private equity firms, or any
combination of these falls under 3 (ii) or 3 (iii) above, see Section
IV. Application and Submission Information for additional instructions
regarding required application certification.

If an Employee Stock Ownership Plan owns all or part of the
concern, each stock trustee and plan member is considered an owner.

If a trust owns all or part of the concern, each trustee and
trust beneficiary is considered an owner.

Definitions:

Hedge fund has the meaning given that term in section 13(h)(2) of
the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The hedge fund
must have a place of business located in the United States and be created or
organized in the United States, or under the law of the United States or of any
State.

Portfolio company means any company that is owned in whole or
part by a venture capital operating company, hedge fund, or private equity
firm.

Private equity firm has the meaning given the term “private
equity fund” in section 13(h)(2) of the Bank Holding Company Act of 1956 (12
U.S.C. 1851(h)(2)). The private equity firm must have a place of business
located in the United States and be created or organized in the United States,
or under the law of the United States or of any State.

Venture capital operating company means an entity described in §
121.103(b)(5)(i), (v), or (vi). The venture capital operating company must have
a place of business located in the United States and be created or organized in
the United States, or under the law of the United States or of any State.

SBCs must also meet the other regulatory requirements found
in 13 C.F.R. Part 121. Business concerns, other than investment companies
licensed, or state development companies qualifying under the Small Business
Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another
when either directly or indirectly, (a) one concern controls or has the power
to control the other; or (b) a third-party/parties controls or has the power to
control both. Business concerns include, but are not limited to, any individual
(sole proprietorship) partnership, corporation, joint venture, association, or
cooperative. The SF424 (R&R) SBIR/STTR Application Guide should be
referenced for detailed eligibility information.

Small
business concerns that are more than 50% owned by multiple venture capital
operating companies, hedge funds, private equity firms, or any combination of
these are NOT eligible to apply to the NIH STTR program.

Phase I to Phase II
Transition Rate Benchmark

In accordance with guidance
from the SBA, the HHS SBIR/STTR Program is implementing the Phase I to Phase II
Transition Rate benchmark required by the SBIR/STTR Reauthorization Act of
2011. This Transition Rate requirement applies to SBIR and STTR
Phase I applicants that have received more than 20 Phase I awards over the past
5 fiscal years, excluding the most recently-completed fiscal year. For
these companies, the benchmark establishes a minimum number of Phase II awards
the company must have received for a given number of Phase I awards received
during the 5-year time period in order to be eligible to receive a new Phase I
award. This requirement does not apply to companies that have received 20
or fewer Phase I awards over the 5 year period.

Companies that apply for a
Phase I award and do not meet or exceed the benchmark rate will not be eligible
for a Phase I award for a period of one year from the date of the application
submission. The Transition Rate is calculated as the total number of SBIR
and STTR Phase II awards a company received during the past 5 fiscal years
divided by the total number of SBIR and STTR Phase I awards it received during
the past 5 fiscal years excluding the most recently-completed year. The
benchmark minimum Transition Rate is 0.25.

SBA calculates individual
company Phase I to Phase II Transition Rates daily using SBIR and STTR award
information across all federal agencies. For those companies that have
received more than 20 Phase I awards over the past 5 years, SBA posts the
company transition rates on the Company Registry at SBIR.gov.
Information on the Phase I to Phase II Transition Rate requirement is available
at SBIR.gov.

Applicants to this FOA that
may have received more than 20 Phase I awards across all federal SBIR/STTR
agencies over the past five (5) years should, prior to application preparation,
verify that their company’s Transition Rate on the Company Registry at SBIR.gov
meets or exceeds the minimum benchmark rate of 0.25.

Phase
II to Phase III Commercialization Benchmark

In accordance with guidance from the SBA, HHS, including
NIH, SBIR/STTR Programs are implementing the Phase II to Phase III Commercialization
Rate benchmark for Phase I applicants, as required by the SBIR/STTR
Reauthorization Act of 2011. The Commercialization Rate Benchmark was published
in a Federal Register notice on August 8, 2013 (78 FR
48537).

This requirement applies to companies that have received
more than 15 Phase II awards from all agencies over the past 10 years,
excluding the two most recently-completed Fiscal Years. Companies that meet
this criterion must show an average of at least $100,000 in revenues and/or
investments per Phase II award or at least 0.15 (15%) patents per Phase II
award resulting from these awards. This requirement does not apply to companies
that have received 15 or fewer Phase II awards over the 10 year period,
excluding the two most recently-completed Fiscal Years.

Information on the Phase II
to Phase III Commercialization Benchmark is available at SBIR.gov.

Applicants to this FOA that
may have received more than 15 Phase II awards across all federal SBIR/STTR
agencies over the past ten (10) years should, prior to application preparation,
verify that their company’s Commercialization Benchmark on the Company Registry
at SBIR.gov meets or exceeds the benchmark rate listed above.

Applicants that fail this
benchmark will be notified by SBA annually and will not be eligible to receive
New Phase I, Fast-track or Direct Phase II awards for a period of one year.

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in
the NIH Grants Policy Statement, may be allowed.

Required Registrations

Applicant
Organizations

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet Universal
Numbering System (DUNS) - All registrations require that applicants be
issued a DUNS number. After obtaining a DUNS number, applicants can begin both
SAM, SBA Company registry, and eRA Commons registrations. The same DUNS number
must be used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually.
The renewal process may require as much time as the initial registration. SAM
registration includes the assignment of a Commercial and Government Entity
(CAGE) Code for domestic organizations which have not already been assigned a
CAGE Code.

SBA Company Registry –See Section IV. Application and Submission
Information, “SF424(R&R) Other Project Information Component” for
instructions on how to register and how to attach proof of registration to your
application package. Applicants must have a DUNS number to complete this
registration. SBA Company registration is NOT required before SAM, Grants.gov or
eRA Commons registration.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants must have an active DUNS number and SAM registration in order to
complete the Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.
PD(s)/PI(s) should work with their organizational officials to either
create a new account or to affiliate their existing account with the applicant
organization in eRA Commons. If the PD/PI is also the organizational Signing
Official, they must have two distinct eRA Commons accounts, one for each role.
Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Under the SBIR program, for both Phase I and Phase II, the
primary employment of the PD/PI must be with the small business concern at the
time of award and during the conduct of the proposed project. For projects with
multiple PDs/PIs, at least one must meet the primary employment requirement.
Occasionally, deviations from this requirement may occur.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept similar grant applications with
essentially the same research focus from the same applicant organization. This
includes derivative or multiple applications that propose to develop a single
product, process, or service that, with non-substantive modifications, can be
applied to a variety of purposes. Applicants may not simultaneously
submit identical/essentially identical applications under both this funding
opportunity and any other HHS funding opportunity, including the SBIR and STTR
Parent announcements.

The NIH will not accept duplicate or highly overlapping
applications under review at the same time. This means that the NIH will
not accept:

A new (A0) application that is submitted before issuance of the
summary statement from the review of an overlapping new (A0) or resubmission
(A1) application.

A resubmission (A1) application that is submitted before issuance
of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another
application pending appeal of initial peer review (see NOT-OD-11-101).

A Phase I awardee may submit a Phase II application either
before or after expiration of the Phase I budget period, unless the awardee
elects to submit a Phase I and Phase II application concurrently under the
Fast-Track procedure. To maintain eligibility to seek Phase II or IIB support,
a Phase I awardee should submit a Phase II application, and a Phase II awardee
should submit a Phase IIB application, within the first six due dates following
the expiration of the Phase I or II budget period, respectively.

Contractual/Consortium Arrangements

In Phase I, normally, a minimum of two-thirds or 67% of the
research or analytical effort must be carried out by the small business
concern. The total amount of all consultant and contractual arrangements to
third parties for portions of the scientific and technical effort generally may
not exceed 33% of the total amount requested (direct, F&A/indirect, and
fee).

In Phase II, normally, a minimum of one-half or 50% of the research or
analytical effort must be carried out by the small business concern. The total
amount of consultant and contractual arrangements to third parties for portions
of the scientific and technical effort generally may not exceed 50% of the
total Phase II amount requested (direct, F&A/indirect, and fee).

A small business concern may subcontract a portion of its
SBIR or STTR award to a Federal laboratory within the limits above. A Federal
laboratory, as defined in 15 U.S.C. § 3703, means any laboratory, any federally
funded research and development center, or any center established under 15
U.S.C. §§ 3705 & 3707 that is owned, leased, or otherwise used by a Federal
agency and funded by the Federal Government, whether operated by the Government
or by a contractor.

The basis for determining the percentage of work to be
performed by each of the cooperative parties in Phase I or Phase II will be the
total of the requested costs attributable to each party, unless otherwise
described and justified in “Consortium/Contractual Arrangements” of the PHS 398
Research Plan component of SF424 (R&R) application forms.

Buttons to access the online ASSIST system or to download
application forms are available in Part
1 of this FOA. See your administrative office for instructions if you plan
to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the SBIR/STTR (B) Instructions
in the SF424
(R&R) SBIR/STTR Application Guide, including Supplemental
Grant Application Instructions except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

All page limitations described in the SF424 (R&R) SBIR/STTR
Application Guide and the Table of
Page Limits must be followed.

Instructions
for Application Submission

The following section supplements the instructions found in
the SF 424 (R&R) SBIR/STTR Application Guide and should be used for
preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) SBIR/STTR
Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) SBIR/STTR
Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) SBIR/STTR
Application Guide must be followed, with the following additional instructions:

Other
Attachments:

1. SBA Company registry

All applicants to the SBIR and STTR programs are required to
register at the SBA Company Registry prior to application
submission and attach proof of registration. Completed registrations will
receive a unique SBC Control ID and .pdf file. If applicants have previously
registered, you are still required to attach proof of registration. The SBA
Company Registry recommends verification with SAM, but a SAM account is
not required to complete the registration. In order to be verified with SAM,
your email address must match one of the contacts in SAM. If you are unsure
what is listed in SAM for your company, you may verify the information on the
SAM site. Confirmation of your company's DUNS is necessary to verify your email
address in SAM. Follow these steps listed below to register and attach proof of
registration to your application.

b. If you are a
previous SBIR/STTR awardee from any agency, search for your small business by
Company Name, EIN/Tax ID, DUNS, or Existing SBIR/STTR Contract/Grant Number in
the search fields provided. Identify your company and click “Proceed to
Registration”.

d. Fill out the
required information on the “Basic Information” and “Eligibility Statement”
screens.

e. Press “Complete
Registration” on the lower right of the “Eligibility Statement” screen and
follow all instructions.

f. Download
and save your SBA registry PDF locally. The name will be in the format of
SBC_123456789.pdf, where SBC_123456789 (9 digit number) is your firm’s SBC
Control ID. DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may
cause delays in the processing of your application.

g. When you are
completing the application package, attach this SBA registry PDF as a separate
file by clicking "Add Attachments" located to the right of the Other
Attachments field on the “Research and Related Other Project Information” form.

Applicant small business concerns that are majority-owned by
multiple venture capital operating companies, hedge funds, or private equity
firms (e.g., majority VCOC-owned) are required to submit a Certification at
time of their application submission per the SBIR Policy Directive.
Follow the instructions below.

Applicants from small business concerns which are more than
50% directly owned and controlled by one or more individuals (who are citizens
or permanent resident aliens of the United States), other business concerns
(each of which is more than 50% directly owned and controlled by individuals
who are citizens or permanent resident aliens of the United States), or any
combination of these (i.e., NOT majority VCOC-owned) should NOT fill out this
certification and should NOT attach it their application package.

d. Save the
certification using the original file name. The file must be named “SBIR Application
VCOC Certification.pdf”. DO NOT CHANGE OR ALTER THE FILE NAME. Changing the
file name may cause delays in the processing of your application.

e. When you are
completing the application package, attach this certification as a separate
file by clicking "Add Attachments" located to the right of Other
Attachments field on the “Research and Related Other Project Information” form.

SF424(R&R) Senior/Key Person Profile Expanded

All instructions in the SF424 (R&R) SBIR/STTR
Application Guide must be followed.

R&R Budget

All instructions in the SF424 (R&R) SBIR/STTR
Application Guide must be followed.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) SBIR/STTR
Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) SBIR/STTR Application
Guide must be followed, with the following additional instructions:

Resource
Sharing Plans: Individuals are required to comply with the
instructions for the Resource Sharing Plans as provided in the SF424 (R&R)
SBIR/STTR Application Guide, .

Appendix:

Do not use the Appendix to circumvent page limits. The
instructions for the Appendix of the Research Plan are described in the SF424
(R&R) Application Guide.

Note that Phase I SBIR/STTR Appendix materials are not
permitted.

PHS Inclusion Enrollment Report

Form only available in FORMS-D application packages for use with due dates on or before January 24, 2018.

When conducting clinical research, follow all instructions
for completing PHS Inclusion Enrollment Report as described in the SF424
(R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) SBIR/STTR
Application Guide must be followed.

3. Unique Entity Identifier
and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the
requirement for obtaining a unique entity identifier and for completing and
maintaining active registrations in System for Award Management (SAM), SBA
Company Registry, eRA Commons, and Grants.gov.

4. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates and time. Applicants are encouraged to
submit applications before the due date to ensure they have time to make any
application corrections that might be necessary for successful submission. When
a submission date falls on a weekend or Federal
holiday, the application deadline is automatically extended to the next
business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the
application due date and time. If a Changed/Corrected application is submitted
after the deadline, the application will be considered late. Applications that
miss the due date and time are subjected to the NIH Policy on Late Application
Submission.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) SBIR/STTR Application
Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically. If you encounter a system issue beyond your control that
threatens your ability to complete the submission process on-time, you must
follow the Guidelines
for Applicants Experiencing System Issues. For assistance with application submission, contact
the Application Submission Contacts in Section
VII.

Important reminders:

All PD(s)/PI(s) must include their
eRA Commons ID in the Credential field of the Senior/Key Person Profile
Component of the SF424(R&R) Application Package. Failure to register in the
Commons and to include a valid PD/PI Commons ID in the credential field will
prevent the successful submission of an electronic application to NIH.

The applicant organization must
ensure that the DUNS number it provides on the application is the same number
used in the organization’s profile in the eRA Commons and for the System for
Award Management (SAM). Additional information may be found in the SF424
(R&R) SBIR/STTR Application Guide.

Applicants are required to follow the instructions for
post-submission materials, as described in the policy.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an
important problem or a critical barrier to progress in the field? Is there
a strong scientific premise for the project? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change
the concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field? Does the proposed project have commercial
potential to lead to a marketable product, process or service? (In the case of
Phase II, Fast-Track, and Phase II Competing Renewals, does the
Commercialization Plan demonstrate a high probability of commercialization?)

Investigator(s)

Are the PD(s)/PI(s), collaborators,
and other researchers well suited to the project? If Early Stage Investigators
or
those in the early stages
of independent careers, do they
have appropriate experience and training? If established, have they
demonstrated an ongoing record of accomplishments that have advanced their
field(s)? If the project is collaborative or multi-PD/PI, do the investigators
have complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and
seek to shift current research or clinical practice paradigms by utilizing
novel theoretical concepts, approaches or methodologies, instrumentation, or
interventions? Are the concepts, approaches or methodologies, instrumentation,
or interventions novel to one field of research or novel in a broad sense? Is a
refinement, improvement, or new application of theoretical concepts, approaches
or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy,
methodology, and analyses well-reasoned and appropriate to accomplish the
specific aims of the project? Have
the investigators presented strategies to ensure a robust and unbiased
approach, as appropriate for the work proposed? Are potential problems,
alternative strategies, and benchmarks for success presented? If the project is
in the early stages of development, will the strategy establish feasibility and
will particularly risky aspects be managed? Have the investigators presented
adequate plans to address relevant biological variables, such as sex, for
studies in vertebrate animals or human subjects?

If the project involves human
subjects and/or NIH-defined clinical research, are the plans to address 1) the
protection of human subjects from research risks, and 2) inclusion (or
exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as
well as the inclusion or exclusion of children, justified in terms of the
scientific goals and research strategy proposed?

Environment

Will the scientific environment in
which the work will be done contribute to the probability of success? Are the
institutional support, equipment and other physical resources available to the
investigators adequate for the project proposed? Will the project benefit from
unique features of the scientific environment, subject populations, or
collaborative arrangement?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Phase II
Applications

For Phase II Applications, how well
did the applicant demonstrate progress toward meeting the Phase I objectives,
demonstrating feasibility, and providing a solid foundation for the proposed
Phase II activity?

1. Does the Phase I application
specify clear, appropriate, measurable goals (milestones) that should be
achieved prior to initiating Phase II?

2. To what extent was the applicant
able to obtain letters of interest, additional funding commitments, and/or
resources from the private sector or non-SBIR/STTR funding sources that would
enhance the likelihood for commercialization?

Protections
for Human Subjects

For research that involves human
subjects but does not involve one of the six categories of research that are
exempt under 45 CFR Part 46, the committee will evaluate the justification for
involvement of human subjects and the proposed protections from research risk
relating to their participation according to the following five review
criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3)
potential benefits to the subjects and others, 4) importance of the knowledge
to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human
subjects and meets the criteria for one or more of the six categories of
research that are exempt under 45 CFR Part 46, the committee will evaluate: 1)
the justification for the exemption, 2) human subjects involvement and
characteristics, and 3) sources of materials. For additional information on
review of the Human Subjects section, please refer to the Guidelines for the Review of Human
Subjects.

Inclusion
of Women, Minorities, and Children

When the proposed project involves
human subjects and/or NIH-defined clinical research, the committee will
evaluate the proposed plans for the inclusion (or exclusion) of individuals on
the basis of sex/gender, race, and ethnicity, as well as the inclusion (or
exclusion) of children to determine if it is justified in terms of the
scientific goals and research strategy proposed. For additional information on
review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion
in Clinical Research.

Vertebrate
Animals

The committee will evaluate the
involvement of live vertebrate animals as part of the scientific assessment
according to the following criteria: (1) description of proposed procedures
involving animals, including species, strains, ages, sex, and total number to
be used; (2) justifications for the use of animals versus alternative models
and for the appropriateness of the species proposed; (3) interventions to
minimize discomfort, distress, pain and injury; and (4) justification for
euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia
of Animals. Reviewers will assess the use of chimpanzees as they would any
other application proposing the use of vertebrate animals. For additional
information on review of the Vertebrate Animals section, please refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether
materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Resubmissions

For Resubmissions, the committee
will evaluate the application as now presented, taking into consideration the
responses to comments from the previous scientific review group and changes
made to the project.

Phase IIB
Competing Renewals

For Phase IIB Applications, the
committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will
consider the appropriateness of the proposed expansion of the scope of the project.
If the Revision application relates to a specific line of investigation
presented in the original application that was not recommended for approval by
the committee, then the committee will consider whether the responses to
comments from the previous scientific review group are adequate and whether
substantial changes are clearly evident.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Select Agent
Research

Reviewers will assess the
information provided in this section of the application, including 1) the
Select Agent(s) to be used in the proposed research, 2) the registration status
of all entities where Select Agent(s) will be used, 3) the procedures that will
be used to monitor possession use and transfer of Select Agent(s), and 4) plans
for appropriate biosafety, biocontainment, and security of the Select Agent(s).

For projects involving key
biological and/or chemical resources, reviewers will comment on the brief plans
proposed for identifying and ensuring the validity of those resources.

Budget and
Period of Support

Reviewers will consider whether the
budget and the requested period of support are fully justified and reasonable
in relation to the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) , in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a committee process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Applications will be assigned on the basis of established
PHS referral guidelines to the appropriate NIH Institute or Center. Applications
will compete for available funds with all other recommended applications. Following
initial peer review, recommended applications will receive a second level of
review by the appropriate National Advisory Council or Board. The following
will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons. Refer to
Part 1 for dates for peer review, advisory council review, and earliest start
date

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA)
will be provided to the applicant organization for successful applications. The
NoA signed by the grants management officer is the authorizing document and
will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described
in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be
subject to terms and conditions found on the Award
Conditions and Information for NIH Grants website. This includes any recent
legislation and policy applicable to awards that is highlighted on this website.

Recipients of federal financial
assistance (FFA) from HHS must administer their programs in compliance with
federal civil rights law. This means that recipients of HHS funds must ensure
equal access to their programs without regard to a person’s race, color,
national origin, disability, age and, in some circumstances, sex and religion.
This includes ensuring your programs are accessible to persons with limited
English proficiency. HHS recognizes that research projects are often limited
in scope for many reasons that are nondiscriminatory, such as the principal
investigator’s scientific interest, funding limitations, recruitment
requirements, and other considerations. Thus, criteria in research protocols
that target or exclude certain populations are warranted where
nondiscriminatory justifications establish that such criteria are appropriate
with respect to the health or safety of the subjects, the scientific study
design, or the purpose of the research.

For additional guidance regarding how the provisions apply
to NIH grant programs, please contact the Scientific/Research Contact that is
identified in Section VII under Agency Contacts of this FOA. HHS provides
general guidance to recipients of FFA on meeting their legal obligation to take
reasonable steps to provide meaningful access to their programs by persons with
limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html.
The HHS Office for Civil Rights also provides guidance on complying with civil
rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html;
and http://www.hhs.gov/ocr/civilrights/understanding/index.html.
Recipients of FFA also have specific legal obligations for serving qualified
individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
Please contact the HHS Office for Civil Rights for more information about
obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS
Departmental goal to ensure access to quality, culturally competent care,
including long-term services and supports, for vulnerable populations. For
further guidance on providing culturally and linguistically appropriate
services, recipients should review the National Standards for Culturally and
Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in
Section 872 of the Duncan Hunter National Defense Authorization Act of
Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to
theFederal Awardee Performance and Integrity Information System
(FAPIIS) requirements. FAPIIS requires Federal award making officials to
review and consider information about an applicant in the designated integrity
and performance system (currently FAPIIS) prior to making an award. An
applicant, at its option, may review information in the designated integrity
and performance systems accessible through FAPIIS and comment on any
information about itself that a Federal agency previously entered and is
currently in FAPIIS. The Federal awarding agency will consider any comments by
the applicant, in addition to other information in FAPIIS, in making a
judgement about the applicant’s integrity, business ethics, and record of
performance under Federal awards when completing the review of risk posed by
applicants as described in 45 CFR Part 75.205 “Federal awarding agency review
of risk posed by applicants.” This provision will apply to all NIH grants and
cooperative agreements except fellowships.

Report fraud, waste and abuse

The Office of Inspector General Hotline
accepts tips from all sources about potential fraud, waste, abuse and
mismanagement in Department of Health & Human Services programs. The
reporting individual should indicate that the fraud, waste and/or abuse
concerns an SBIR/STTR grant or contract, if relevant. Report Fraud.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

NIH requires that SBIR/STTR grantees submit the following
reports within 90 days of the end of the grant budget period unless the grantee
is under an extension. When multiple years are involved, awardees will be
required to submit the Research
Performance Progress Report (RPPR) annually and financial statements as
required in the NIH Grants
Policy Statement.

Failure to submit timely final reports may affect future
funding to the organization or awards with the same PD/PI.

For details about each specific required report, see Part
III. Section 5, "SBIR/STTR Award Guidelines, Reporting Requirements, and
Other Considerations,” in the Supplement Grant Applications For All Competing
Applications and Progress Reports.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statementfor additional information on this
reporting requirement.

In accordance with the regulatory requirements provided at
45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have
currently active Federal grants, cooperative agreements, and procurement
contracts from all Federal awarding agencies with a cumulative total value
greater than $10,000,000 for any period of time during the period of
performance of a Federal award, must report and maintain the currency of
information reported in the System for Award Management (SAM) about civil,
criminal, and administrative proceedings in connection with the award or
performance of a Federal award that reached final disposition within the most
recent five-year period. The recipient must also make semiannual disclosures
regarding such proceedings. Proceedings information will be made publicly
available in the designated integrity and performance system (currently
FAPIIS). This is a statutory requirement under section 872 of Public Law
110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public
Law 111-212, all information posted in the designated integrity and performance
system on or after April 15, 2011, except past performance reviews required for
Federal procurement contracts, will be publicly available. Full reporting
requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award
Term and Conditions for Recipient Integrity and Performance Matters.

Section
VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284) and under
Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

The SBIR Program is mandated by the Small Business
Innovation Development Act of 1982 (P.L. 97-219), reauthorizing legislation
(P.L. 99-443) P.L. 102-564, and P.L. 112-81 (SBIR/STTR Reauthorization Act of
2011). The basic design of the NIH SBIR Program is in accordance with the Small
Business Administration (SBA) SBIR Policy
Directive.